ubiquitin-dependent protein catabolic process

Definition

Target type: biologicalprocess

The chemical reactions and pathways resulting in the breakdown of a protein or peptide by hydrolysis of its peptide bonds, initiated by the covalent attachment of a ubiquitin group, or multiple ubiquitin groups, to the protein. [GOC:go_curators]

Ubiquitin-dependent protein catabolic process is a fundamental cellular process responsible for the selective degradation of proteins. It plays a crucial role in maintaining cellular homeostasis by removing misfolded or damaged proteins, regulating protein levels, and controlling signaling pathways. This process involves a cascade of enzymatic reactions that tag target proteins with ubiquitin, a small protein, leading to their recognition and degradation by the proteasome, a large protein complex.

The ubiquitin-dependent protein catabolic process begins with the activation of ubiquitin by the E1 enzyme, an ubiquitin-activating enzyme. This process involves the ATP-dependent binding of ubiquitin to E1, forming a high-energy thioester bond. The activated ubiquitin is then transferred to an E2 enzyme, an ubiquitin-conjugating enzyme. The E2 enzyme, in turn, transfers the ubiquitin to the target protein, which is facilitated by an E3 enzyme, an ubiquitin ligase.

E3 ligases are highly specific and recognize specific target proteins based on their degradation signal, typically a short amino acid sequence. The E3 ligase brings the target protein and the ubiquitin-charged E2 enzyme together, allowing the transfer of ubiquitin to the target protein. This process is repeated multiple times, resulting in the formation of a polyubiquitin chain on the target protein.

Polyubiquitin chains act as a signal for the proteasome, a barrel-shaped protein complex responsible for protein degradation. The proteasome recognizes the polyubiquitin chain and unfolds the target protein, feeding it into the proteasome's central chamber, where it is degraded into small peptides. The ubiquitin chains are then removed and recycled.

The ubiquitin-dependent protein catabolic process is highly regulated and plays a critical role in various cellular functions, including:

* **Protein quality control:** Removal of misfolded or damaged proteins prevents their accumulation, which can lead to cellular dysfunction.
* **Cellular signaling:** Degradation of signaling proteins can regulate the duration and intensity of signaling pathways.
* **Cell cycle control:** Degradation of key cell cycle regulators ensures proper progression through the cell cycle.
* **Immune response:** Degradation of antigens and other molecules involved in the immune response is essential for immune regulation.
* **Developmental processes:** Degradation of specific proteins is crucial for proper development and differentiation.

Dysregulation of the ubiquitin-dependent protein catabolic process can lead to various diseases, including cancer, neurodegenerative disorders, and inflammatory diseases. Understanding the intricacies of this process is crucial for developing new therapies to treat these diseases.'
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Proteins (21)

Compounds (77)